PROJECT SUMMARY (ADMIN CORE) The Clinical Genome Resource (ClinGen) is a collaborative project focused on building the world?s best resource for clinical grade annotation of human genomic variation. During the first phase of this project, the three funded grants worked closely with each other and NCBI/ClinVar to accomplish our shared goals. This included developing an administrative structure and establishment of a steering committee, external advisory committee, and more than a dozen working groups covering topics that include informatics and technology infrastructure, patient engagement, professional education, and, of course, dedicated clinical domain working groups that included cardiovascular disease, inborn errors of metabolism, pharmacogenomics, hereditary cancer, neonatal screening programs, and the ACMG set of genes where incidental findings are considered clinically actionable . During the first phase of the project, these working groups prioritized genes within their domain and we developed associated resources designed for gene::disease and variant curation as well as modeling and data warehousing. The resource was designed with the goal of scaling up of curation as we seek to support whole genome clinical-grade annotation of know pathogenic (and non-pathogenic) variants across the spectrum of characterized and (novel) genetic disorders. To enable this scale up, we are proposing additional working groups, community resources, and administrative practices that will ensure our success. The last of these is described in detail in the first Aim of this section which covers the Management and Administration of ClinGen and the organization of our individual Stanford/Baylor component. Briefly, our team has worked very well together and we will retain our Multi-PI structure with Dr. Plon heading our interactions with the clinical domain working groups and Dr. Bustamante overseeing the development of informatics resources. We have also contributed to the overall projected by providing the backbone infrastructure to enable gene::disease and variant curation, data warehousing and integration, and development of novel computational predictors for missense and regulatory variation. The management of the Gene and Variant Curation Interfaces (GCI/VCI) as well as Allele Registry, Pathogenicity Calculator, and Actionability Curation are discussed in Aim 2. These are established programs run by Dr. Cherry and Dr. Milosavljevic with dedicated professional staff and user engagement to request, design, and test new features. Our informatics team is also embedded across clinical domain working groups (CDWGs) as well as data modeling, variant interpretation, and software alignment committees. This ensures that the resource we build is responsive to the overall project as well as our individual user needs. Our final Aim, describes the education and outreach efforts we propose. This includes video tutorials, workshops, webinars, discussion forums, documentation, and other user support. The web portal has been previously described and broad dissemination of resources is discussed Resource Sharing section of this application.